Animal model systems are useful tools for identifying and characterizing therapeutic agents. Examples of such model systems are transgenic animal models with brain tumors. Currently, there are several transgenic animal models that recapitulate key features of human primitive neuroectodermal tumors (PNET) (Fung, K. M., and Trojanowski, J. Q., (1995) Animal models of medulloblastomas and related primitive neuroectodermal tumors. A review. J. Neuropathol. Exp. Neurol. 54, 285–296). Members of each of these transgenic animal lines develop PNETs arising in different, yet distinct, brain regions. However, the animals in these four transgenic lines also have some features in common, namely the expression of the neuronal cell marker synaptophysin (Fung, K. M., Chikaraishi, D. M., Suri, C., Theuring, F., Messing, A., Albert, D. M., Lee, V. M., Trojanowski, J. Q. (1994). Molecular phenotype of simian virus 40 large T antigen-induced primitive neuroectodermal tumors in four different lines of transgenic mice. Lab. Invest. 70, 114124). The presence of this cell marker indicates that these tumors are derived from cells that have differentiated beyond the earliest stages of neural stem cells.
It is desirable to have additional animal models for identifying agents which are effective at preventing, slowing or reversing the growth of brain tumors. It is especially desirable to have an animal whose brain tumor cells are at an early stage of differentiation, i.e., the tumor cells have not yet progressed to the stage where they are expressing markers that are indicative of neurons (synaptophysin and neuron-specific enolase), astrocytes (glial fibrillary acidic protein and S-100), or oligodendrocytes (galactocerebroside).